title: PHACOS, a functionalized bacterial polyester with bactericidal activity against methicillin-resistant Staphylococcus aureus.
abstract: Biomaterial-associated infections represent a significant clinical problem, and treatment of these microbial infections is becoming troublesome due to the increasing number of antibiotic-resistant strains. Here, we report a naturally functionalized bacterial polyhydroxyalkanoate (PHACOS) with antibacterial properties. We demonstrate that PHACOS selectively and efficiently inhibits the growth of methicillin-resistant Staphylococcus aureus (MRSA) both in vitro and in vivo. This ability has been ascribed to the functionalized side chains containing thioester groups. Significantly less (3.2-fold) biofilm formation of S. aureus was detected on PHACOS compared to biofilms formed on control poly(3-hydroxyoctanoate-co-hydroxyhexanoate) and poly(ethylene terephthalate), but no differences were observed in bacterial adhesion among these polymers. PHACOS elicited minimal cytotoxic and inflammatory effects on murine macrophages and supported normal fibroblast adhesion. In vivo fluorescence imaging demonstrated minimal inflammation and excellent antibacterial activity for PHACOS compared to controls in an in vivo model of implant-associated infection. Additionally, reductions in neutrophils and macrophages in the vicinity of sterile PHACOS compared to sterile PHO implant were observed by immunohistochemistry. Moreover, a similar percentage of inflammatory cells was found in the tissue surrounding sterile PHACOS and S. aureus pre-colonized PHACOS implants, and these levels were significantly lower than S. aureus pre-colonized control polymers. These findings support a contact active surface mode of antibacterial action for PHACOS and establish this functionalized polyhydroxyalkanoate as an infection-resistant biomaterial.
authors.affiliation: Centro de Investigaciones Biológicas, CSIC, Madrid 28040, Spain.
authors.forename: Nina
authors.initials: N
authors.lastname: Dinjaski
authors.forename: Mar
authors.initials: M
authors.lastname: Fernández-Gutiérrez
authors.forename: Shivaram
authors.initials: S
authors.lastname: Selvam
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Parra-Ruiz
authors.forename: Susan M
authors.initials: SM
authors.lastname: Lehman
authors.forename: Julio
authors.initials: J
authors.lastname: San Román
authors.forename: Ernesto
authors.initials: E
authors.lastname: García
authors.forename: José L
authors.initials: JL
authors.lastname: García
authors.forename: Andrés J
authors.initials: AJ
authors.lastname: García
authors.forename: María Auxiliadora
authors.initials: MA
authors.lastname: Prieto
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001419:Bacteria / Q000737:chemistry*; D018441:Biofilms; D002448:Cell Adhesion / Q000187:drug effects; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D051379:Mice; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D011091:Polyesters / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D011091:Polyesters
keywords: Antimicrobial polymers; Biofilm; Biomaterial infection; Functionalized polyhydroxyalkanoate; Methicillin-resistant Staphylococcus aureus